Identifying novel acute pancreatitis sub-phenotypes using total serum calcium trajectories.

BACKGROUND: Acute pancreatitis (AP) has heterogeneous clinical features, and identifying clinically relevant sub-phenotypes is useful. We aimed to identify novel sub-phenotypes in hospitalized AP patients using longitudinal total serum calcium (TSC) trajectories. METHODS: AP patients had at least two TSC measurements during the first 24 h of hospitalization in the US-based critical care database (Medical Information Mart for Intensive Care-III (MIMIC-III) and MIMIC-IV were included. Group-based trajectory modeling was used to identify calcium trajectory phenotypes, and patient characteristics and treatment outcomes were compared between the phenotypes. RESULTS: A total of 4518 admissions were included in the analysis. Four TSC trajectory groups were identified: "Very low TSC, slow resolvers" (n = 65; 1.4% of the cohort); "Moderately low TSC" (n = 559; 12.4%); "Stable normal-calcium" (n = 3875; 85.8%); and "Fluctuating high TSC" (n = 19; 0.4%). The "Very low TSC, slow resolvers" had the lowest initial, maximum, minimum, and mean TSC, and highest SOFA score, creatinine and glucose level. In contrast, the "Stable normal-calcium" had the fewest ICU admission, antibiotic use, intubation and renal replace treatment. In adjusted analysis, significantly higher in-hospital mortality was noted among "Very low TSC, slow resolvers" (odds ratio [OR], 7.2; 95% CI, 3.7 to 14.0), "moderately low TSC" (OR, 5.0; 95% CI, 3.8 to 6.7), and "Fluctuating high TSC" (OR, 5.6; 95% CI, 1.5 to 20.6) compared with the "Stable normal-calcium" group. CONCLUSIONS: We identified four novel sub-phenotypes of patients with AP, with significant variability in clinical outcomes. Not only the absolute TSC levels but also their trajectories were significantly associated with in-hospital mortality.

Novel anthropometric indicators of visceral obesity predict the severity of hyperlipidemic acute pancreatitis.

BACKGROUND: Obesity substantially contributes to the onset of acute pancreatitis (AP) and influences its progression to severe AP. Although body mass index (BMI) is a widely used anthropometric parameter, it fails to delineate the distribution pattern of adipose tissue. To circumvent this shortcoming, the predictive efficacies of novel anthropometric indicators of visceral obesity, such as lipid accumulation products (LAP), cardiometabolic index (CMI), body roundness index (BRI), visceral adiposity index (VAI), A Body Shape Index (ABSI), and Chinese visceral adiposity index (CVAI) were examined to assess the severity of AP. METHOD: The body parameters and laboratory indices of 283 patients with hyperlipidemic acute pancreatitis (HLAP) were retrospectively analysed, and the six novel anthropometric indicators of visceral obesity were calculated. The severity of HLAP was determined using the revised Atlanta classification. The correlation between the six indicators and HLAP severity was evaluated, and the predictive efficacy of the indicators was assessed using area under the curve (AUC). The differences in diagnostic values of the six indicators were also compared using the DeLong test. RESULTS: Patients with moderate to severe AP had higher VAI, CMI, and LAP than patients with mild AP (all P < 0.001). The highest AUC in predicting HLAP severity was observed for VAI, with a value of 0.733 and 95% confidence interval of 0.678-0.784. CONCLUSIONS: This study demonstrated significant correlations between HLAP severity and VAI, CMI, and LAP indicators. These indicators, particularly VAI, which displayed the highest predictive power, were instrumental in forecasting and evaluating the severity of HLAP.

Anemia can predict organ failure in acute pancreatitis

Acute pancreatitis (AP) is the leading hospital admission in Gastroenterology and has a variable clinical course. Identifying severity of AP patients in its early stages is of foremost importance to improve prognosis. The revised Atlanta Classification grades AP severity by the presence of organ failure and local complications. (AU)

Predictive Value of Serum NGAL and B2 Microglobulin in Blood and Urine amongst Patients with Acute Pancreatitis and Acute Kidney Injury

Objective: This study aimed to explore the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) and β2 microglobulin (β2-MG) in blood and urine amongst patients with acute pancreatitis (AP) and acute kidney injury (AKI). Methods: The clinical data of 80 patients with AP, who were treated in the study hospital from November 2019, to November 2022, were selected for retrospective analysis. They were divided into AKI group (n = 25) and non-AKI group (n = 55) in accordance with the presence of AKI. The levels of serum NGAL and β2-MG in blood and urine were compared in both groups. Logistic regression analysis was used to explore the influencing factors of AKI in patients with AP and the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of serum NGAL and β2-MG in the blood and urine of patients with AKI and AP. Results: The AKI group had higher serum NGAL and β2-MG in blood and urine than the non-AKI group. Logistic regression analysis showed that the high levels of serum NGAL and β2-MG in blood and urine were risk factors for AKI in patients with AP (p < 0.05). The areas under the curve (AUC), sensitivity and specificity of the combined prediction were 0.97, 84.00% and 98.20%, respectively, showing a good prediction efficiency. Conclusions: The increased levels of serum NGAL and β2-MG in blood and urine have a warning significance for patients with AP and AKI and a certain predictive value. So, their combination detection provides a reliable reference for the identification of clinical AKI (AU)

[Predictive value of serum chlorine and interleukin-6 combined with coagulation indexes on severity of severe acute pancreatitis].

OBJECTIVE: To explore the predictive value of combined detection of serum interleukin-6 (IL-6), chloride (Cl-), D-dimer and fibrin degradation products (FDP) for severity of acute pancreatitis (AP). METHODS: From December 2020 to March 2022, 132 AP patients who met the criteria for inclusion were screened for retrospective analysis from 292 AP patients admitted in emergency surgery at the First Affiliated Hospital of Zhengzhou University and they were divided into severe acute pancreatitis (SAP) group and non-SAP group, with 63 in SAP group and 69 in non-SAP group, according to classification criteria. The data including lab results, abdominal doppler ultrasound and chest and abdominal CT, etc. The bedside index for severity in acute pancreatitis (BISAP) score was calculated. Multivariate Logistic regression analysis was carried out to find the risk factors for the severity of AP patients. The receiver operator characteristic curve (ROC) was drawn to judge the clinical predictive value of each factor. RESULTS: A total of 132 AP patients were enrolled. The serum IL-6, D-dimer, FDP levels and the BISAP score in SAP group were significantly higher than those in non-SAP group [serum IL-6 (ng/L): 62.73 (21.54, 187.47) vs. 8.22 (4.13, 14.70), D-dimer (mg/L): 5.36 (2.94, 8.25) vs. 0.94 (0.42, 2.21), FDP (mg/L): 13.54 (6.76, 22.45) vs. 3.20 (2.50, 6.10), BISAP score: 2.00 (1.00, 3.00) vs. 1.00 (0, 2.00), all P < 0.05], while the serum Cl- level was significantly lower than that of non-SAP group (mmol/L: 97.90±4.86 vs. 101.73±4.32, P < 0.05). Multivariate Logistic regression analysis showed that increased levels of IL-6 [odds ratio (OR) = 1.02, 95% confidence interval (95%CI) was 1.01-1.04], D-dimer (OR = 1.21, 95%CI was 1.05-1.40) and decreased Cl- level (OR = 0.88, 95%CI was 0.79-0.98) were risk factors for SAP (all P < 0.05). The ROC curve analysis showed that the area under the ROC curve (AUC) of IL-6, Cl-, D-dimer and FDP combined to predict the severity of AP patients was larger (0.89), and the sensitivity (82.50%) and specificity (85.50%) were higher. CONCLUSIONS: Compared with single index, the combined detection of serum IL-6, Cl-, D-dimer and FDP is more precise in determining the condition of AP.

Upregulation of B7-H4 Is Involved in and Related to the Severity of Acute Pancreatitis.

The expression and clinical significance of co-stimulator B7-H4 in acute pancreatitis (AP) is still unclear. In vitro study showed that the expression of soluble B7-H4 (sB7-H4) and proportions of membrane B7-H4-positive CD14+ cells in the peripheral blood mononuclear cells were upregulated in response to stimulation with plasma from AP patients, lipopolysaccharides, or tumor necrosis factor α (TNF-α). sB7-H4 in the plasma of AP patients were positively correlated with interleukin (IL)-6, IL-10, IL-17A, TNF-α, and interferon-γ The areas under the curves (AUCs) of receiver operating characteristic (ROC) curves of plasma sB7-H4 to distinguish the AP patients from healthy donors, the mild AP (MAP) from the moderately severe acute pancreatitis (MSAP)+severe acute pancreatitis (SAP) or the SAP from the MAP+MSAP were 0.78 (P < 0.001) or 0.773 (P < 0.001) or 0.764 (P < 0.001). sB7-H4 in the plasma of patients were positively correlated with the RANSON scores, Bedside Index of Severity of Acute Pancreatitis scores, Marshall scores, and Acute Physiology And Chronic Health Evaluation II scores; and the AUCs of ROC curves of plasma sB7-H4 in the prediction of local complications was 0.726 (P = 0.001). In conclusion, the co-stimulator B7-H4 is involved in the immune response in AP.

Impact of hemolysis on multi-OMIC pancreatic biomarker discovery to derisk biomarker development in precision medicine studies.

Cancer biomarker discovery is critically dependent on the integrity of biofluid and tissue samples acquired from study participants. Multi-omic profiling of candidate protein, lipid, and metabolite biomarkers is confounded by timing and fasting status of sample collection, participant demographics and treatment exposures of the study population. Contamination by hemoglobin, whether caused by hemolysis during sample preparation or underlying red cell fragility, contributes 0-10 g/L of extraneous protein to plasma, serum, and Buffy coat samples and may interfere with biomarker detection and validation. We analyzed 617 plasma, 701 serum, and 657 buffy coat samples from a 7-year longitudinal multi-omic biomarker discovery program evaluating 400+ participants with or at risk for pancreatic cancer, known as Project Survival. Hemolysis was undetectable in 93.1% of plasma and 95.0% of serum samples, whereas only 37.1% of buffy coat samples were free of contamination by hemoglobin. Regression analysis of multi-omic data demonstrated a statistically significant correlation between hemoglobin concentration and the resulting pattern of analyte detection and concentration. Although hemolysis had the greatest impact on identification and quantitation of the proteome, distinct differentials in metabolomics and lipidomics were also observed and correlated with severity. We conclude that quality control is vital to accurate detection of informative molecular differentials using OMIC technologies and that caution must be exercised to minimize the impact of hemolysis as a factor driving false discovery in large cancer biomarker studies.

Correlation Between Severity of Illness and Levels of Free Triiodothyronine, Interleukin-6, and Interleukin-10 in Patients with Acute Pancreatitis.

BACKGROUND Acute pancreatitis (AP) is a common acute abdominal disease. Rapid evaluation of the severity is important for AP prognosis and treatment. Free triiodothyronine (fT3) level is associated with the prognosis of AP patients. This study aimed to investigate the fT3 level in patients with acute pancreatitis; early warning signs of inflammation, including interleukin-6 (IL-6) and interleukin-10 (IL-10); and the correlation of fT3 level with illness severity. MATERIAL AND METHODS Enrolled AP patients (N=312) were divided into an SAP group (N=92) and a non-SAP group (N=220) according to the Revision of Atlanta classification. Blood or tissue samples and baseline clinical characteristics were recorded. The t test and chi-square test were used to evaluate differences between the 2 groups. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to investigate protective factors. One-way repeated measures analysis of variance was used to evaluate the prognosis of SAP patients. RESULTS In our study, compared with APACHII score (AUC 0.829 [95% CIs 0.769-0.889]) and Ranson score (AUC 0.629 [95% CIs 0.542-0.715]), our predictive model (AUC 0.918 [95% CIs 0.875-0.961]) showed better prognostic performance in predicting poor patient outcomes. In the SAP group, changes in fT3 level were significantly associated with prognosis (P<0.05). CONCLUSIONS The predictive model can improve the diagnostic accuracy and prediction of the severity of disease. FT3 level could be used as an independent risk factor to predict the mortality of SAP patients.

Association of genetic variants in the GPX1 and GPX4 genes with the activities of glutathione-dependent enzymes, their interaction with smoking and the risk of acute pancreatitis.

Genetic factors and tobacco smoke exposure can be associated with an increased risk of acute pancreatitis (AP). The pathogenesis of AP is associated with intensive oxidative stress. Glutathione peroxidase (GPx) is one of many enzymes involved in the neutralization of free radicals. This study aimed to investigate the impact of SNP rs1050450 in the GPX1 gene and rs713041 in the GPX4 gene on the activity of total GPx in a group of AP patients and healthy subjects. It was found that AP can contribute to decreased GPx activity (in plasma and erythrocyte lysate) accompanied by an increased glutathione reductase (GR) activity and decreased glutathione (GSH) concentration in two groups, non-smokers and smokers. A decreased GPx activity in erythrocyte lysate of AP patients compared to healthy subjects was associated with the occurrence of the CC genotype for SNP rs1050450. It was noted an increased GPx activity and decreased GR activity in erythrocytes of non-smoking AP patients with the TT genotype compared to subjects with the CC and TC genotype for SNP rs713041. However, in the group of smoking AP patients with this genotype, GR activity was elevated compared to non-smokers, which was accompanied by increased GSH concentration. These results can indicate that smoking in the course of AP can change the involvement of antioxidants in dependence on the genotype for the examined SNPs. The CC genotype for SNP rs1050450 and the TT genotype for rs713041 increases the risk of AP recurrence, which may be associated with increased MDA concentration.

Growth differentiation factor 15 is an early predictor for persistent organ failure and mortality in acute pancreatitis.

OBJECTIVES: Early prediction of persistent organ failure (POF) is crucial for patients with acute pancreatitis (AP). Growth differentiation factor 15 (GDF15), also known as macrophage inhibitory cytokine 1 (MIC-1), is associated with inflammatory responses. We investigated changes in plasma GDF15 and assessed its predictive value in AP. METHODS: The study included 290 consecutive patients with AP admitted within 36 h after symptoms onset. Clinical data obtained during hospitalization were collected. Plasma GDF15 levels were determined using enzyme-linked immunosorbent assays. The predictive value of GDF15 for POF was analyzed. RESULTS: There were 105 mild, 111 moderately severe, and 74 severe AP patients. Plasma GDF15 peak level were measured on admission, and significantly declined on the 3rd and 7th day. Admission GDF15 predicted POF and mortality with areas under the curve (AUC) of 0.847 (95% confidence interval [CI] 0.798-0.895) and 0.934 (95% CI 0.887-0.980), respectively. Admission GDF15, Bedside Index of Severity in Acute Pancreatitis, and hematocrit were independent factors for POF by univariate and multivariate logistic regression, and the nomogram built on these variables showed good performance (optimism-corrected c-statistic = 0.921). The combined predictive model increased the POF accuracy with an AUC 0.925 (95% CI 0.894-0.956), a net reclassification improvement of 0.3024 (95% CI: 0.1482-0.4565, P < 0.001), and an integrated discrimination index of 0.11 (95% CI 0.0497-0.1703; P < 0.001). CONCLUSIONS: Plasma GDF15 measured within 48 h of symptom onset could help predict POF and mortality in AP patients.

Early postoperative serum hyperamylasemia: Harbinger of morbidity hiding in plain sight?

BACKGROUND: The clinical significance of postoperative serum pancreatic enzyme elevation after pancreatoduodenectomy is understudied. We hypothesized that elevation in serum enzymes predicts morbidity and mortality after pancreatoduodenectomy. METHODS: Retrospective review of 677 patients who underwent pancreatoduodenectomy at a single institution from 2013 to 2019. Patients were categorized based on serum enzyme concentrations. Patient characteristics, drain amylase, and outcomes among groups were compared. RESULTS: In total, 415 of 677 patients had postoperative serum amylase concentrations measured. Of these, 243 (59%) were normal, 96 (23%) were classified as postoperative serum hyperamylasemia, and 76 (18%) were classified as postoperative acute pancreatitis. Major morbidity was lower among patients with normal enzyme concentration (10%) and higher in patients with postoperative serum hyperamylasemia (23%) and postoperative acute pancreatitis (18%) (P = .008). Patients with normal enzymes were less likely to develop postoperative pancreatic fistula (5%) compared with patients with postoperative serum hyperamylasemia (26%) and postoperative acute pancreatitis (21%) (P < .001) and less likely to develop delayed gastric emptying (9% vs 23% and 20%, respectively); P = .002. No difference in mortality was seen among groups. CONCLUSION: Elevated serum pancreatic enzyme concentration occurs frequently after pancreatoduodenectomy and is associated with increased postoperative morbidity. Serum enzyme concentration should be considered in management after pancreatoduodenectomy.

Hypogelsolinemia and Decrease in Blood Plasma Sphingosine-1-Phosphate in Patients Diagnosed with Severe Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a frequent hospitalization cause of patients suffering from gastrointestinal disorders. Gelsolin has an ability to bind bioactive lipids including different sphingolipids engaged in inflammatory response. Importantly, hypogelsolinemia was observed in patients with different states of acute and chronic inflammation. AIMS: The aim of the present study was to assess the interplay of blood plasma gelsolin and blood plasma sphingosine-1-phosphate (S1P) concentration in patients diagnosed with acute pancreatitis. MATERIALS AND METHODS: To assess the concentration of gelsolin and S1P, immunoblotting and HPLC technique were employed, respectively. Additionally, the concentrations of amylase, lipase, C-reactive protein (CRP), procalcitonin (PCT) and the number of white blood cells (WBC) and platelet (PLT) were recorded. RESULTS: We found that both pGSN and S1P concentrations in the plasma of the AP patients were significantly lower (pGSN ~ 15-165 mg/L; S1P ~ 100-360 pmol/mL) when compared to the levels of pGSN and S1P in a control group (pGSN ~ 130-240 mg/L; S1P ~ 260-400 pmol/mL). Additionally, higher concentrations of CRP, WBC, amylase and lipase were associated with low level of gelsolin in the blood of AP patients. No correlations between the level of PCT and PLT with gelsolin concentration were noticed. CONCLUSION: Plasma gelsolin and S1P levels decrease during severe acute pancreatitis. Simultaneous assessment of pGSN and S1P can be useful in development of more accurate diagnostic strategies for patients with severe acute pancreatitis.

Establishing the blood reference interval of pancreatic elastase-1: A prospective study.

BACKGROUND AND AIM: Pancreatic elastase-1 (PE-1) has been investigated in pancreatic disorders. However, the reference interval (RI) of PE-1 in blood remains unconfirmed. We aimed to establish the blood RI of PE-1 in an adult population. METHODS: In this prospective cross-sectional study, we enrolled 400 adults who had received the whole-body physical check-up program between May 1, 2019 and November 20, 2019. The serum and plasma PE-1 levels were measured by latex turbidimetric immunoassay in different storage conditions (fresh, refrigerated, and frozen). The 95% and 99% RI of PE-1 were calculated according to the Clinical & Laboratory Standards Institute guidelines. The correlations between PE-1 and other parameters were analyzed using multivariable regression models. Ultimately, 38 patients with acute pancreatitis were prospectively recruited as the validation cohort. RESULTS: The PE-1 levels in fresh serum were highly correlated with those in refrigerated (R2  = 0.998) or frozen (R2  = 0.942) samples; however, plasma should not be suggested in frozen conditions (plasma vs serum: R2  = 0.185). In the RI study population (202 male & 198 female participants), the median age was 52.6 (25-75% interquartile range: 43.1-61.0). The 95% and 99% RIs of PE-1 were 30.0-221.0 and 22.0-359.0 ng/dL, respectively. Triglycerides (ß = 0.106, P = 0.033), lipase (ß = 0.154, P = 0.007), and CA19-9 (ß = 0.130, P = 0.008) were independent factors associated with PE-1. In the pancreatitis validation cohort, with a cut-off value of 359.0 ng/dL, the sensitivity and specificity were 100% and 99.8%, respectively. CONCLUSION: The RI of PE-1 established in this study can be used for further applications. Serum is the suggested form for frozen sample storage.

Application of a complete blood count to screening lethargic and anorectic cats for pancreatitis.

BACKGROUND: Feline pancreatitis (FP) is an important health problem of cats. Its diagnostics is based on the combination of quantification of serum pancreatic lipase immunoreactivity (fPLI) and abdominal ultrasonography (AUS). These modalities allow for establishing highly specific diagnosis, however they are relatively expensive and time-consuming. On the other hand, a screening test of high sensitivity which would allow to rule out FP on the first visit without a considerable increase of costs would be clinically useful. To evaluate accuracy of nonspecific inflammatory biomarkers based on complete blood count (CBC) in diagnosing FP 73 client-owned cats with signs of lethargy and reduced appetite lasting for at least 2 days before presentation were enrolled in the cross-sectional study. They were examined with fPLI assay and AUS and classified as cats with very low risk of FP when fPLI ≤3.5 µg/L and AUS negative for FP, or as cats with increased risk of FP in the case of any other combination of results. Then, 7 various CBC measurements were measured in each cat and linked to the risk of FP using the multivariable logistic regression. RESULTS: Five CBC measurements turned out to be significantly associated with the risk of FP - total leukocyte count (WBC; crude odds ratio(ORcrude) = 12.2; CI 95%: 1.52, 98.5), total neutrophil count (ORcrude = 5.84; CI 95%: 1.22, 27.9), band neutrophil count (BNC; ORcrude = 6.67; CI 95%: 1.98, 22.4), neutrophil-to-lymphocyte ratio (ORcrude = 3.68; CI 95%: 1.25, 10.9), and eosinophil count (EC; ORcrude = 0.34; CI 95%: 0.12, 0.96). The model based on WBC, BNC, and EC proved to have at least fair diagnostic potential (area under ROC curve 82.7%; CI 95%: 72.8%, 92.5%). When WBC <  18 G/L, BNC <  0.27 G/L, and EC >  0.3 G/L was considered as a negative result, and any other combination as the positive result, the CBC model had high sensitivity (91.8%; CI 95%: 80.8%, 96.8%) at a relatively low specificity (58.3%; CI 95%: 38.8%, 75.5%). CONCLUSION: The combination of three CBC measurements is an immediately available and fairly accurate screening method for identification of lethargic and anorectic cats with increased risk of FP.

Hypoalbuminemia affects one third of acute pancreatitis patients and is independently associated with severity and mortality.

The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (< 35 g/L) was 19% on admission and 35.7% during hospitalization. Hypoalbuminemia dose-dependently increased the risk of severity, mortality, local complications and organ failure and is associated with longer hospital stay. The predictive value of hypoalbuminemia on admission was poor for severity and mortality. Severe hypoalbuminemia (< 25 g/L) represented an independent risk factor for severity (OR 48.761; CI 25.276-98.908) and mortality (OR 16.83; CI 8.32-35.13). Albumin loss during AP was strongly associated with severity (p < 0.001) and mortality (p = 0.002). Hypoalbuminemia represents an independent risk factor for severity and mortality in AP, and it shows a dose-dependent relationship with local complications, organ failure and length of stay.

Circulating CitH3 Is a Reliable Diagnostic and Prognostic Biomarker of Septic Patients in Acute Pancreatitis.

Purpose: Acute pancreatitis (AP) is an inflammatory disease. AP starts with sterile inflammation and is often complicated with critical local or systemic infection or sepsis in severe cases. Septic AP activates peptidyl arginine deiminase (PAD) and citrullinates histone H3 (CitH3), leading to neutrophil extracellular trap (NET) formation. Investigating the role of NETs and underlying mechanisms in septic AP may facilitate developing diagnostic and therapeutic approaches. In this study, we sought to identify the expression of CitH3 in septic AP patients and to analyze the correlation of CitH3 concentration with NET components as well as clinical outcomes. Methods: Seventy AP patients with or without sepsis (40 septic cases, 30 nonseptic cases) and 30 healthy volunteers were recruited in this study. Concentration of NET components (CitH3 and double-strain DNA) and key enzymes (PAD2/4) were measured. Clinical and laboratory characteristics of patients were recorded and analyzed. Results: Levels of CitH3 were elevated significantly in septic AP patients compared with those in nonseptic AP and healthy volunteers. The area under the curve (AUC, 95% confidence interval) for diagnosing septic AP was 0.93 (0.86-1.003), and the cutoff was 43.05 pg/ml. Among septic AP cases (n = 40), the concentration of CitH3 was significantly increased in those who did not survive or were admitted to the intensive care unit, when compared with that in those who survived or did not require intensive care unit. Association analysis revealed that CitH3 concentration was positively correlated with PAD2, PAD4, dsDNA concentration, and Sequential Organ Failure Assessment scores. Conclusion: CitH3 concentration increased in septic AP patients and was closely correlated with disease severity and clinical outcomes. CitH3 may potentially be a diagnostic and prognostic biomarker of septic AP.

Analysis of Outcomes in COVID-19 Patients With Varying Degrees of Hyperlipasemia.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) patients may have varying degrees of hyperlipasemia. The aim was to compare outcomes among different levels of hyperlipasemia in patients with COVID-19. METHODS: This is a retrospective study examining outcomes among hospitalized COVID-19 patients with a lipase <3× upper limit of normal (ULN), asymptomatic hyperlipasemia (>3× ULN), secondary pancreatitis (typical respiratory COVID-19 symptoms and found to have pancreatitis), and primary pancreatitis (presenting with pancreatitis). RESULTS: Of 11,883 patients admitted with COVID-19, 1560 patients were included: 1155 patients had normal serum lipase (control group), 270 had elevated lipase <3× ULN, 46 patients had asymptomatic hyperlipasemia with lipase >3× ULN, 57 patients had secondary pancreatitis, and 32 patients had primary pancreatitis. On adjusted multivariate analysis, the elevated lipase <3× ULN and asymptomatic hyperlipasemia groups had worse outcomes with higher mortality (odds ratio [OR], 1.6 [95% confidence interval [CI], 1.2-2.2) and 1.1 [95% CI, 0.5-2.3], respectively), higher need for mechanical ventilation (OR, 2.8 [95% CI, 1.2-2.1] and 2.8 [95% CI, 1.5-5.2], respectively), and longer length of stay (OR, 1.5 [95% CI, 1.1-2.0] and 3.16 [95% CI, 1.5-6.5], respectively). CONCLUSIONS: Patients with COVID-19 with elevated lipase <3× ULN and asymptomatic hyperlipasemia have generally worse outcomes than those with pancreatitis.

The BISAP score, NLR, CRP, or BUN: Which marker best predicts the outcome of acute pancreatitis?

ABSTRACT: Acute pancreatitis is a common disease, and the mortality rate can be high. Thus, a risk assessment should be performed early to optimize treatment. We compared simple prognostic markers with the bedside index for severity in acute pancreatitis (BISAP) scoring system to identify the best predictors of severity and mortality.This retrospective study stratified disease severity based on the revised Atlanta criteria. The accuracies of the markers for predicting severe AP (SAP) were assessed using receiver operating characteristic curves. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each marker. Multivariate logistic regression analyses were used to identify independent predictors of SAP and mortality.The area under the curve (AUC) for the BISAP score was classified as fair for predicting SAP. The neutrophil-to-lymphocyte ratio at 48 hours (NLR48 h) and the C-reactive protein level at 48 hours (CRP48 h) had the best AUCs and were independently associated with SAP. When both criteria were met, the AUC was 0.89, sensitivity was 68%, and specificity was 92%. CRP48 h and hematocrit at 48 hours were independently associated with mortality.NLR48 h and CRP48 h were independently associated with SAP but not superior to the BISAP score at admission. Assessing NLR48 h and CRP48H together was most suitable for predicting SAP. The CRP level was a good predictive marker for mortality.

Chymase as a Novel Therapeutic Target in Acute Pancreatitis.

Acute pancreatitis is still a life-threatening disease without an evidenced therapeutic agent. In this study, the effect of chymase in acute pancreatitis and the possible effect of a chymase inhibitor in acute pancreatitis were investigated. Hamsters were subcutaneously administered 3.0 g/kg of L-arginine to induce acute pancreatitis. Biological markers were measured 1, 2, and 8 h after L-arginine administration. To investigate the effect of a chymase inhibitor, a placebo (saline) or a chymase inhibitor TY-51469 (30 mg/kg) was given 1 h after L-arginine administration. The survival rates were evaluated for 24 h after L-arginine administration. Significant increases in serum lipase levels and pancreatic neutrophil numbers were observed at 1 and 2 h after L-arginine administration, respectively. Significant increases in pancreatic neutrophil numbers were observed in the placebo-treated group, but they were significantly reduced in the TY-51469-treated group. A significant increase in the pancreatic tumor necrosis factor-α mRNA level was observed in the placebo-treated group, but it disappeared in the TY-51469-treated group. Chymase activity significantly increased in the placebo-treated group, but it was significantly reduced by treatment with TY-51469. The survival rate significantly improved in the TY-51469-treated group. A chymase inhibitor may become a novel therapeutic agent for acute pancreatitis.

Hypertriglyceridemia-associated acute pancreatitis: Response to continuous insulin infusion.

OBJECTIVE: To assess the response of serum triglycerides (TG) to continuous insulin infusion (CII) in adults with hypertriglyceridemia-associated acute pancreatitis (HTGP). METHODS: Retrospective analysis of TG response to standardized CII therapy in 77 adults admitted to intensive care with TG >1000 mg/dL and HTGP. RESULTS: Participants had initial TG 3869.0 [2713.5, 5443.5] mg/dL and were 39.3 ± 9.7 years old, 66.2% males, 58.4% Hispanic, BMI 30.2 [27.0, 34.8] kg/m2, 74.0% with diabetes mellitus (DM) and 50.6% with excess alcohol use. TG-goal, defined as ≤1,000 ± 100 mg/dL, was achieved in 95%. Among the 73 TG-goal achievers (responders), 53.4% reached TG-goal in <36 hours after CII initiation (rapid responders). When compared to slow responders taking≥36 hours, rapid responders had lower initial TG (2862.0 [1965.0, 4519.0] vs 4814.5 [3368.8, 6900.0] mg/dL), BMI (29.4 [25.9, 32.8] vs 31.9 [28.2, 38.3] kg/m2), DM prevalence (56.4 vs 94.1%), and reached TG-50% (half of respective initial TG) faster (12.0 [6.0, 17.0] vs 18.5 [13.0, 32.8] hours). Those with DM (n = 57) vs non-DM (n = 20) were obese (31.4 [28.0, 35.6] vs 27.8 [23.6, 30.3] kg/m2), took longer to reach TG-final (41.0 [25.0, 60.5] vs 14.5 [12.5, 25.5] hours) and used more daily insulin (1.7 [1.3, 2.1] vs 1.1 [0.5, 1.9] U/kg/day). Among those with DM, the rapid responders had higher daily use of insulin vs slow responders 1.9 [1.4, 2.3] vs 1.6 [1.1, 1.8] U/kg/day. All results significant. In multivariable analysis, predictors of faster TG response were absence of DM, lower BMI and initial TG. CONCLUSION: CII was effective in reaching TG-goal in 95% of patients with HTGP. Half achieved TG-goal within 36 hours. Presence of DM, higher BMI and initial TG slowed the time to reach TG-goal. These baseline parameters and rate of decline to TG-50% may be real-time indicators to initiate and adjust the CII for quicker response.